Interleukin-1 beta-induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: Amagnetic resonance study

The cytokine interleukin-1 beta (IL-1 beta) is implicated in a broad spectr um of CNS pathologies, in which it is thought to exacerbate neuronal loss. Here, the effects of injecting recombinant rat IL-1 beta into the striatum of 3-week-old rats were followed noninvasively from 2 to 123 hr using magne tic resonance imaging and spectroscopy. Four hours after injection of IL-1 beta (1 ng in 1 mul), cerebral blood volume was significantly increased, th e blood-brain barrier (BBB) became permeable to intravenously administered contrast agent between 4.5 and 5 hr, and the apparent diffusion coefficient (ADC) of brain water fell by 6 hr (5.42 +/- 0.35 x 10(-4) mm(2)/sec treate d, 7.35 +/- 0.77 x 10(-4) mm(2)/sec control; p < 0.001). At 24 hr the BBB w as again intact, but the ADC, although partially recovered, remained depres sed at both 24 and 123 hr ( p < 0.03). Depleting the animals of neutrophils before IL-1 beta injection prevented the BBB permeability at all time poin ts, but the ADC was still depressed at 6 hr (6.64 +/- 0.34 x 10(-4) mm(2)/s ec treated, 7.49 +/- 0.38 x 10(-4) mm(2)/sec control; p < 0.005). No change s were seen in brain metabolites using proton spectroscopy at 6 hr after IL -1<beta>. Intraparenchymal injection of IL-1 beta caused a neutrophil-dependent trans ient increase in BBB permeability. The presence of neutrophils within the b rain parenchyma significantly contributed to the IL-1 beta -induced changes in cerebral blood volume and the ADC of brain water. However, IL-1 beta ap parently had a direct effect on the resident cell populations, which persis ted well after all recruited leukocytes had disappeared. Thus the action of IL-1 beta alone can give rise to magnetic resonance imaging-visible change s that are normally attributed to alterations to cellular homeostasis.